The metabolic and lipid profiles of horses treated with sodium-glucose cotransporter 2 inhibitors are not well understood. This retrospective study evaluated blood parameters in hyperinsulinemic horses treated with either ertugliflozin (0.05 mg/kg) or dapagliflozin (0.02 mg/kg) orally once daily. Blood samples were collected at baseline (day 0) and after 7 and/or 30 days of treatment. Statistical analyses were conducted using Wilcoxon signed-rank, Mann-Whitney and Spearman's rank correlation tests. Thirty-four horses received dapagliflozin and 24 received ertugliflozin. Significant (p<0.05) within-horse changes between day 0 and day 30 included [median, inter-quartile range (IQR)]: basal serum [Insulin] (uU/ml) reduced 170 (92-280) to 28.7 (14.5-90); [triglycerides] (mmol/l) increased 0.5 (0.3-0.6) to 1.0 (0.6-1.56), [β-hydroxybutyrate] (umol/l) increased 0.22 (0.17-2.7) to 0.30 (0.24-0.35); [total cholesterol] (mmol/l) increased 2.36 (2-2.6) to 2.84 (2.4-3.7); and GGT (IU/ml) increased 21 (16-32) to 25 (18-38). As a percentage of total serum lipids, high-density lipoprotein (HDL) reduced 52.4% (47.9%-61.0%) to 50% (41%-54.8%) and very-low density lipoprotein (VLDL) increased 10.4% (6.4%-14.4%) to 12.3% (9.9%-16.8%) (all p<0.05). Differences between ertugliflozin and dapagliflozin groups were not significant in any of these parameters at days 0, 7 or 30. At day 30, 10/48 (21%) cases had [triglycerides] > 2.0mmol/l (maximum = 10.8mmol/l). Day 30 [triglyceride] correlated with day 0: basal insulin (rho=0.47); [triglyceride] (rho=0.42); %VLDL (rho=0.34) day 30: [total cholesterol] (rho=0.67), %HDL (rho=-0.432) and %VLDL (rho=0.708). Our findings suggest that SGLT2 inhibitors induce minor changes in lipid profiles, with occasional cases of marked hypertriglyceridemia, and that dapagliflozin and ertugliflozin exhibit similar biochemical effects.

Summary Background Preliminary evidence indicates that ertugliflozin benefits horses and ponies (hereafter collectively referred to as horses) with hyperinsulinaemia and hyperinsulinaemia‐associated laminitis. The effects of ertugliflozin on the results of the oral sugar test used widely in the assessment of insulin dysregulation (ID), have not been reported. Objectives To report the effects of ertugliflozin on responses to the oral sugar test (OST) in horses with ID. Study design Retrospective case series. Methods Clinical records were reviewed to identify horses with ID that had an OST (0.45 mL/kg Karo‐Light PO) performed before and after 4 days of treatment with 0.05 mg/kg ertugliflozin PO s.i.d. Pre‐ and post‐treatment insulin concentrations were compared using Wilcoxon sign‐ranked tests. Results Ten horses with ID met the inclusion criteria. Significant reductions in plasma insulin concentration were identified at all time points after 4 days of treatment with ertugliflozin relative to pre‐treatment values. At T0 (prior to oral sugar), median insulin concentration reduced from 22.4 μu/mL (IQR: 6.5, 39) pre‐treatment to 4.8 μu/mL (IQR: 3.7, 9.2) at day 4 ( p = 0.004). At T60 (60 min after oral sugar), median insulin concentration was 165 μu/mL (IQR: 61.2, 222) pre‐treatment and 78.1 μu/mL (IQR: 30.5, 137) at day 4 ( p = 0.004). At T90 (90 min after oral sugar), median insulin concentration was 170 μu/mL (IQR: 88.6, 269) pre‐treatment and 84.7 μu/mL (IQR: 28.7, 122) at day 4 ( p = 0.002). Serum triglyceride concentration increased from a median of 0.4 mmol/L (IQR: 0.2, 0.8) pre‐treatment to 0.9 mmol/L (IQR: 0.6, 2) at day 4 of ertugliflozin treatment ( p = 0.006). Main limitations A small heterogenous group of horses and ponies, some with PPID, were used in the absence of a control group. Conclusions Four daily doses of ertugliflozin at 0.05 mg/kg was associated with lowering of insulin concentrations at baseline and in response to an OST in horses with ID; however, insulin levels did not return to normal in all horses. Increases in triglyceride concentrations were also observed.

Summary Laminitis associated with hyperinsulinaemia is a significant cause of morbidity and mortality in horses with equine metabolic syndrome. The diagnosis and management of hyperinsulinaemia are therefore critical to prevent the development of laminitis. This review article aims to help primary care clinicians manage patients with hyperinsulinaemia by providing an overview of diagnostics, management strategies and new therapies that are available.

SummaryBackgroundSodium‐glucose cotransporter 2 inhibitors (SGLT2i) are being used increasingly in equine practice. While there is emerging clinical evidence of the safety and efficacy of these drugs, there are currently no reports to document owner experiences with treatment.ObjectiveThe objective of the study was to report owner experiences and observations following treatment with SGLT2i in horses.Study designA cross‐sectional online survey.MethodsHorse owners were recruited via social media, online forums and their veterinarians to participate in an anonymous online survey to document their experiences and observations when treating their horses with SGLT2i.ResultsThree hundred forty‐two responses met the inclusion criteria. Ertugliflozin was the most commonly prescribed SGLT2i (79.8%), and the most common reasons for treatment were high insulin concentrations (84.2%) and active laminitis (59.7%). 85.3% of owners reported their horses had an improved quality of life after commencing treatment, while 9.4% reported no change and 5.3% reported a worsening of clinical signs. Of owners who had considered euthanasia prior to treatment (n = 77), 80.5% reported their horse's level of pain to be either mild or absent after 30 days of treatment and 94.8% reported their horse's quality of life to be improved. Most owners (n = 220, 64.7%) reported they were either extremely satisfied or somewhat satisfied (n = 72, 21.2%) with treatment. Treatment concerns included safety/side effects, medication cost, availability and long‐term efficacy. 114 owners (33.3%) reported one or more initial adverse effects upon induction onto the medication, particularly excessive urination (n = 70, 20.5%), excessive drinking (n = 38, 11.1%), excessive weight loss (n = 34, 9.9%) and dullness (n = 26, 7.6%).Main limitationSampling bias through social media and veterinary practices and reliance on subjective owner reports.ConclusionThe use of SGLT2i in horses was associated with excellent rates of owner satisfaction and owner‐reported improved quality of life for the horse; however, some adverse effects were observed.

Laminitis associated with hyperinsulinemia a significant cause of morbidity and mortality in horses with equine metabolic syndrome. The diagnosis and management of insulin dysregulation are therefore critical to prevent the development of hyperinsulinemia-associated laminitis. This review article aims to help primary care clinicians manage patients with insulin dysregulation by providing an overview of diagnostics, management strategies and new therapies that are available.

David Rendle provides consultancy services to BOVA UK and BOVA Aus who produce ertugliflozin for use in horses and to other companies who produce equine therapeutics. Tania Sundra has received travel and accommodation expenses for attendance at CPD events from BOVA Aus. Data sharing is not applicable to this article as no new data were created or analysed in this study.

Exercise-induced pulmonary hemorrhage (EIPH) occurs commonly in horses undergoing strenuous exercise. Reported risk factors include racing in cold temperatures and wearing of bar shoes. In horses with documented moderate to severe EIPH, increasing the interval between races and adopting a negative race pace strategy may reduce the severity of EIPH in subsequent races. EIPH seems to have an impact on performance only when moderate to severe. This occurs in a small number of starters, approximately 6%. EIPH often is erratic in severity from race to race, although across a population it is weakly progressive over increasing race starts.

Summary Primary peritonitis in horses attributable to Actinobacillus equuli has been reported in Australia, New Zealand and North America. Published reports describe a rapid response to treatment with appropriate antimicrobial and supportive treatment and an excellent prognosis for survival. To our knowledge, this is the first reported case of Actinobacillus capsulatus in the horse. The case was complicated by the development of an idiopathic chylous abdominal effusion. The report highlights the importance of molecular methods in the correct identification of bacterial species. Prognosis for horses diagnosed with Actinobacillus peritonitis may be guarded given the atypical response to appropriate antimicrobial treatment in this case.

OBJECTIVE:To investigate the relationship between bronchoalveolar lavage fluid cytology, particularly mast cells, and airway hyper-reactivity in athletic horses presented for poor performance that included a respiratory tract evaluation in two disparate locations in Australia. DESIGN:Multi-centre, retrospective and prospective cross-sectional study METHODS: Eighty four adult horses underwent both pulmonary function testing and histamine bronchoprovocation with a commercial flowmetric plethysmography system. A bronchoalveolar lavage was performed four to twelve hours later. Bronchoalveolar lavage fluid cytology was categorised using two differing classification systems to define mild equine asthma. Statistical analysis was used to assess associations between bronchoalveolar lavage fluid relative inflammatory cell percentages, and airway hyper-reactivity and their associated categorisations. RESULTS:Sixty four percent (54/84) of horses displayed airway hyper-reactivity, as defined by PC35 < 6 mg/ml of histamine. A relative mastocytosis was the most common bronchoalveolar lavage fluid cytological abnormality. Horses with a sole mast cell response of ≥ 5% within their bronchoalveolar lavage fluid displayed airway hyper-reactivity at a lower dose of nebulized histamine than horses with normal bronchoalveolar lavage fluid cytology. Horses with mixed cell responses (relative mast cell percentage > 2% and/or relative neutrophil percentage > 5% and/or eosinophil relative cell percentage ≥ 1%) displayed airway hyper-reactivity at a lower dose of nebulized histamine than horses with normal bronchoalveolar lavage fluid cytology. CONCLUSION:In the Australian context, recently revised increased bronchoalveolar lavage fluid cytology relative cell percentage cut offs appear appropriate for sole mast cell responses. The historical lower cut offs appear to be appropriate for mixed inflammatory cell responses.

Objective To determine the agreement of invasive blood pressure measured in the facial artery, the metatarsal artery and the carotid. Additionally, to evaluate the effects of two haemodynamic conditions on agreement. Study design Prospective, randomized study. Animals Eight horses aged 7 (4 -23) years with a body weight of 493 ± 33 kg. Methods Horses were anaesthetized and positioned in dorsal recumbency. Invasive blood pressure was measured simultaneously via catheters placed in the facial, metatarsal and carotid artery. Cardiovascular function and agreement between arteries was assessed before and during administration of phenylephrine and sodium nitroprusside. These were administered until carotid mean pressure (MAPc) increased or decreased from baseline (65 ± 5 mmHg) to > 90 mmHg or < 50 mmHg, respectively. Data recorded at each sample time included systolic (SAP), mean (MAP) and diastolic (DAP) for carotid (c), facial (f) and metatarsal (m) artery as well as cardiac output (Qt) and systemic vascular resistance (SVR). Bland-Altman analysis was used to assess agreement between peripheral and central sites and regression analysis was used to determine influence of Qt and SVR. Results The largest difference was observed in SAPc and SAPm with a bias and limits of agreement (LOA) of 2 (-15 to 19) mmHg. The bias (LOA) for MAPc and MAPf was 2 (-4 to 9) mmHg and for MAPc and MAPm was 5 (-4 to 14) mmHg. The best agreement for DAP was seen between DAPc and DAPf with bias (LOA) of 1 (-3 to 5) mmHg. Regression analysis indicated marginal influence on agreement by Qt on MAPc and MAPf. Conclusion and clinical relevance The MAP and DAP of the carotid was generally higher compared to the peripheral arteries, which may lead to overzealous treatment of hypotension, albeit maintaining central pressures. Cardiac output and systemic vascular resistance did not largely influence the difference between sites.

OBJECTIVE:To determine agreement between invasive blood pressures measured in three peripheral arteries in anaesthetized horses undergoing elective surgery. STUDY DESIGN:Prospective balanced incomplete block design. ANIMALS:A total of 18 client-owned horses. METHODS:Invasive blood pressure (IBP) was measured simultaneously in one of the following three combinations: 1) transverse facial and facial artery; 2) transverse facial and metatarsal artery; and 3) facial and metatarsal artery. The agreement in blood pressure measured for each combination was performed in six horses. At each sample time, systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures were measured concurrently in each artery, and the mean of three consecutive measurements was recorded. The position of horse, heart rate and use of dobutamine were also recorded. Bland-Altman analysis was used to assess agreement between sites. RESULTS:A total of 54 paired measurements were obtained, with 18 paired measurements from each combination. All paired measurements showed poor and haphazard (nonsystematic) agreement. The widest limit of agreement was 51 mmHg for SAP measured in the facial artery and metatarsal artery, with a bias of -11 mmHg. The smallest limit of agreement was 16 mmHg for MAP measured in the transverse facial and metatarsal artery, with a bias of 1 mmHg. CONCLUSIONS AND CLINICAL RELEVANCE:There was poor and haphazard agreement for SAP, MAP and DAP measured in each pair of peripheral arteries in this study. These results show that blood pressure measured in different peripheral arteries cannot be used interchangeably. This has implications for studies that use IBP as an outcome variable and studies determining agreement between noninvasive blood pressure and IBP measurements in horses under general anaesthesia.

Case report A 7-year-old Clydesdale gelding was referred with a history of progressive lethargy and ventral oedema. The horse developed diarrhoea after treatment with antibiotics by the referring veterinarian. History, clinical signs, imaging and laboratory findings were consistent with hypertrophic cardiomyopathy complicated by antibiotic-associated colitis. Progression of clinical signs prompted euthanasia and the antemortem diagnosis of hypertrophic cardiomyopathy was confirmed at postmortem examination. Conclusion Primary HCM is reported as rare in horses, but specific descriptions are lacking. The history, clinical, laboratory and postmortem findings in this case supported a diagnosis of HCM, complicated by antibiotic-associated colitis.

BACKGROUND:Exercise-induced pulmonary haemorrhage (EIPH) is considered a progressive disease based on histopathology, but it is unknown if tracheobronchoscopic EIPH severity worsens over time. OBJECTIVES:The aim of this study was to examine tracheobronchoscopic EIPH changes over time in a population of Thoroughbred racehorses. A secondary aim was to identify factors that affect changes in tracheobronchoscopic EIPH severity between observations. STUDY DESIGN:Prospective, longitudinal, observational cross-sectional study. METHODS:Thoroughbred racehorses were examined with tracheobronchoscopy no earlier than 30 min after racing. Examinations were recorded and graded blindly by experienced veterinarians using a 0-4 scale. Horses with 2 or more observations were included in the analysis. The association between the previous and current EIPH score was investigated using a linear mixed effect model. Factors associated with transitioning from a lower to a high EIPH grade and vice versa were examined using multiple ordinal regression. A semi-parametric regression model was used to examine progression using the number of career starts as a marker for time. Models were adjusted for potential confounding variables. RESULTS:There were 2974 tracheobronchoscopic examinations performed on 747 horses. Blood was detected in over half of all examinations (55.6%). The population prevalence of EIPH increased as the number of examinations for each horse increased. The preceding EIPH score was significantly associated with the current EIPH score. Significant variables associated with moving between EIPH grades were the number of days since last racing, ambient temperature and weight carried. Tracheobronchoscopic EIPH is mildly progressive over the first thirty career starts. MAIN LIMITATIONS:Enrolment was voluntary. Horses were not followed for their entire career. CONCLUSION:Limiting the number of days in the current racing preparation and spacing races for horses with moderate to severe EIPH may be beneficial for reducing tracheobronchoscopic EIPH severity. The association between ambient temperature and EIPH warrants further investigation.

OBJECTIVE:To characterise the relationship between bronchoalveolar lavage fluid (BALF) cytology and pulmonary function testing with histamine bronchoprovocation (HBP) methods in a population of clinically normal horses. DESIGN:Cross-sectional study METHODS: Clinically normal adult horses (n = 33) underwent pulmonary function testing and HBP with a commercial flowmetric plethysmography system. BAL was performed 1-5 days later. Statistical analysis was used to assess associations between BALF cell concentration, relative inflammatory cell percentages and categorisation, and airway hyper-reactivity (AHR). RESULTS:AHR (PC35  ≤ 8 mg/mL) was demonstrated in 17 (52%) of the horses. Using current definitions, BALF cytology was consistent with inflammatory airway disease in 14 (42%) of the horses and 7 of those demonstrated either mastocytic and/or eosinophilic responses. There was no correlation between total inflammatory cell counts or relative percentage and AHR. No statistical association was found between BALF inflammatory cell categories and AHR. CONCLUSION:A direct association between cytological evidence of airway inflammation and AHR was not identified in this population of clinically normal horses. Determining the presence and measuring inflammatory cell mediators in BALF may more accurately reflect AHR. In addition, normal values for cell proportions in BALF may vary between different populations of horses and more appropriate regional reference ranges should be established.

BACKGROUNDExercise-induced pulmonary haemorrhage (EIPH) is commonly implicated as a cause of poor athletic performance but there is limited and conflicting evidence for this association.OBJECTIVESThe aim of this study was to determine if EIPH, based on endoscopic examination after racing, is associated with a variety of novel and established performance parameters.STUDY DESIGNProspective, observational cross-sectional study.METHODSThoroughbred racehorses competing between 2012 and 2015 were examined on-course no earlier than 30 min after racing. Examinations were recorded and graded blindly by experienced veterinarians using a 0-4 scale. Linear mixed effect models were used for analysis of continuous response variables with horse name incorporated as a random effect to account for repeated sampling and horse variability. Generalised estimating equations were used for analysis of binary responses. Performance variables were examined in 2 models, comparing EIPH grade 0 to grades 1-4, and EIPH grade ≤2 compared with EIPH grades ≥3, controlling race factors that could influence performance.RESULTSThere were 3794 observations collected from 1567 horses. EIPH was detected in 55.1% of observations. Horses with grade 4 EIPH were significantly more likely to have a lower finishing position and finish further behind the winner, less likely to place in the first 3 positions and collect race earnings, collected less earnings per race start and were slower over the last 600 m of the race than horses without EIPH (grade 0). Similar associations were seen in Model 2, with horses with EIPH grade ≥3 having inferior performance when compared to horses with EIPH ≤2.MAIN LIMITATIONSEnrolment was voluntary.CONCLUSIONMild to moderate haemorrhage was not associated with inferior race day performance in this population of Thoroughbred racehorses.

REASONS FOR PERFORMING STUDY:Cardiac output does not always increase with dobutamine administration in anaesthetised horses and information on peripheral perfusion is lacking.OBJECTIVES:To determine the effect of intravenous (i.v.) dobutamine infusion with and without a concurrent 20 mL/kg bodyweight (bwt) bolus of crystalloid fluids on the cardiovascular function of acepromazine premedicated, hypotensive, isoflurane-anaesthetised horses.STUDY DESIGN:Randomised, cross-over experiment.METHODS:A total of 6 horses aged 5-13 years, weighing 464-578 kg were premedicated with acepromazine 0.02 mg/kg bwt and then sedated with xylazine 0.8 mg/kg bwt i.v. Anaesthesia was induced with ketamine 2.2 mg/kg bwt and diazepam 0.08 mg/kg bwt i.v. and maintained with isoflurane, adjusted to achieve a target mean arterial pressure (MAP) (60 mmHg ± 5%) 60 min post-induction of anaesthesia (T0). One of 2 treatments was then given. In treatment D, dobutamine was initially infused at 0.5 μg/kg bwt/min and adjusted to achieve a target MAP (80 mmHg ± 5%) within 30 min of infusion initiation. In treatment D+F dobutamine was administered as described for treatment D, with 20 mL/kg bwt Hartmann's solution infused i.v. over 20 min. Cardiac index (CI), haemoglobin concentration ([Hb]), arterial oxygen content (CaO2 ), oxygen delivery index (DO2 I) and bilateral femoral arterial blood flow (FBF) were recorded at T0, 30 min following dobutamine initiation (T1) and 15 min following dobutamine cessation (T2). Data were analysed using a mixed-effect linear model (P<0.05 considered significant).RESULTS:A significant increase in DO2 I (P = 0.008, T0/T1), CaO2 (P = 0.0002, T0/T1) and [Hb] (P<0.0001, T0/T1) and in CaO2 (P = 0.0005, T1/T2) and [Hb] (P = 0.002,T1/T2) occurred during treatment D. A significant increase in FBF (P = 0.005, upper limb; P = 0.042 lower limb, T0/T1) occurred during treatment D+F. Significant differences between treatments were recorded at T1 ([Hb] P = 0.0001, CaO2 P = 0.0003) and T2 ([Hb] P = 0.013). There was no change in CI during either treatment.CONCLUSIONS:The increase in FBF seen with co-administration of fluids and dobutamine may provide a beneficial effect on muscle compared with the use of dobutamine alone.

REASONS FOR PERFORMING STUDY:Ambient temperature has been identified as a risk factor for exercise-induced pulmonary haemorrhage (EIPH) in racing Thoroughbreds. This warranted a more expansive investigation of climatic conditions on the incidence and severity of EIPH. The impact of other variables such as the type of bit used, tongue ties and nonstandard shoes has not been reported and also warrant investigation.OBJECTIVES:To examine the effect of various climatic variables as contributing risk factors for EIPH. Other previously uninvestigated variables as well as standard track and population factors will also be examined.STUDY DESIGN:Cross-sectional study.METHODS:Thoroughbred racehorses competing at metropolitan racetracks in Perth, Western Australia were examined 30-200 min post race with tracheobronchoscopy. Examination took place at 48 race meetings over a 12 month period. Examinations were graded (0-4), independently by two experienced veterinarians. Univariable analyses were performed and variables with a P<0.25 were entered into a multivariable logistic regression analysis. The analysis was performed twice using the presence of blood (EIPH grade 0 vs. grades ≥1) and EIPH grades ≤1 vs. EIPH grades ≥2 as dependent variables.RESULTS:Exercise-induced pulmonary haemorrhage was diagnosed in 56.6% of observations. Lower ambient temperature was significantly associated with EIPH grades ≥1 (OR 0.95; 95% CI 0.93-0.98) and EIPH grades ≥2 (OR 0.97; 95% CI 0.94-1.0). Bar shoes were significantly associated with EIPH grades ≥1 (OR 6.35; 95% CI 2.17-18.54) and EIPH grades ≥2 (OR 2.72; 95% CI 1.3-5.68). Increasing race distance was significantly associated with EIPH grade ≥1 and increasing lifetime starts was significantly associated with EIPH grade ≥2.CONCLUSIONS:Ambient temperature is a risk factor for EIPH in Thoroughbred racehorses, with lower temperatures associated with increased risk. Bar shoes are a novel risk factor for EIPH in this population.